An autoinflammatory neurological disease due to interleukin 6 hypersecretion

Ettore Salsano, Ambra Rizzo, Gloria Bedini, Loris Bernard, Valentina Dallolio, Sara Volorio, Monica Lazzaroni, Isabella Ceccherini, Dejan Lazarevic, Davide Cittaro, Elia Stupka, Rosina Paterra, Laura Farina, Mario Savoiardo, Davide Pareyson, Francesca L. Sciacca

Research output: Contribution to journalArticlepeer-review


Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they are also characterized by non-neurological manifestations. In this work we studied a 30-year-old man who had a chronic disease characterized by meningitis, progressive hearing loss, persistently raised inflammatory markers and diffuse leukoencephalopathy on brain MRI. He also suffered from chronic recurrent osteomyelitis of the mandible. The hypothesis of an autoinflammatory disease prompted us to test for the presence of mutations in interleukin-1-pathway genes and to investigate the function of this pathway in the mononuclear cells obtained from the patient. Search for mutations in genes associated with interleukin-1-pathway demonstrated a novel NLRP3 (CIAS1) mutation (p.I288M) and a previously described MEFV mutation (p.R761H), but their combination was found to be non-pathogenic. On the other hand, we uncovered a selective interleukin-6 hypersecretion within the central nervous system as the likely pathogenic mechanism. This is also supported by the response to the anti-interleukin-6-receptor monoclonal antibody tocilizumab, but not to the recombinant interleukin-1-receptor antagonist anakinra. Exome sequencing failed to identify mutations in other genes known to be involved in autoinflammatory diseases. We propose that the disease described in this patient might be a prototype of a novel category of autoinflammatory diseases characterized by prominent neurological involvement.

Original languageEnglish
Pages (from-to)29
Number of pages1
JournalJournal of Neuroinflammation
Publication statusAccepted/In press - Feb 21 2013

ASJC Scopus subject areas

  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience
  • Neuroscience(all)


Dive into the research topics of 'An autoinflammatory neurological disease due to interleukin 6 hypersecretion'. Together they form a unique fingerprint.

Cite this